Design, Synthesis And Molecular Docking Of L-Prolinamide Containing Thiazolidine-4-One Ring System As(ACE Inhibitors)

Abstract

The present work started with synthesis of five new Schiffbases containing terminal carboxylic acid (A1-A5) group through the condensation of para amino benzoic acid and para substituted benzaldehydes , these compounds were subjected to cyclization reaction with thioglycolic acid to from 2,3-disubstituted -1,3thiazolidine-4-one containing carboxylic group(B1-B5), these carboxylic acids were converted to corresponding acid chlorides(C1-C8) using thionyl chloride, finally L-prolinamides(D1-D8) were synthesized by reaction of acid chlorides with L-proline acid, TLC was used to monitor the reactions, and spectroscopic methods such asFT-IR, 1H-NMR, and mass spectrometry were used to describe all structures, Molecular docking was used to investigate the inhibitory action of the produced compounds (D1-D8) in the activity of the angiotensin-converting enzyme (ACE), All L-proline amide derivatives showed enzyme inhibitory activity,The derivative D8 at a concentration of (10-2-10-6M) and docking Score (-7.134) Kcal/mole reveal good inhibition potency in vitro ACE-inhibitory tests using human blood samples., the in vitro results were backed up by good binding results in molecular docking investigations, According to molecular docking , The results were compared to Captopril and Enalapril as a reference drug.